Langford P R, Harpur E S, Kayes J B, Gonda I
J Antibiot (Tokyo). 1982 Oct;35(10):1387-93. doi: 10.7164/antibiotics.35.1387.
The electrophoretic mobility of phosphatidyl inositol liposomes at pH 7.4, 25 degrees C, was reduced by aminoglycoside antibiotics, neamine and several polyamines in general accordance with the number of amino-groups on each molecule. There was good agreement between the relative position of the tested compounds on the mobility-concentration graph and available information about their relative mammalian toxicities in vivo. The slope of the graph for netilmicin was distinctively flat; a comparatively flat dose-response curve for netilmicin has been reported also from in vivo studies of nephrotoxicity. Investigation of a homologous series of alpha,omega straight chain diaminoalkanes revealed that hydrophobicity did not contribute significantly to the observed interaction in this system. L-Lysine showed the weakest effect amongst all compounds tested, supporting the view that the overall positive charge on the molecule was the major determinant of the observed effect. Further structure-activity work is required to confirm whether this 'in vitro' test is predictive of the toxicity of aminoglycoside antibiotics in man.
在pH 7.4、25摄氏度条件下，磷脂酰肌醇脂质体的电泳迁移率会被氨基糖苷类抗生素、新霉素以及几种多胺降低，总体上与每个分子上氨基的数量相关。受试化合物在迁移率-浓度图上的相对位置与它们在体内相对哺乳动物毒性的现有信息之间存在良好的一致性。奈替米星的图斜率明显平缓；在肾毒性的体内研究中也报道了奈替米星相对平缓的剂量反应曲线。对一系列α,ω直链二氨基烷烃的研究表明，疏水性对该体系中观察到的相互作用贡献不大。在所有受试化合物中，L-赖氨酸的作用最弱，这支持了分子上的整体正电荷是观察到的效应的主要决定因素这一观点。需要进一步开展构效关系研究，以确认这种“体外”试验是否能预测氨基糖苷类抗生素对人体的毒性。
